Device and method for rapid aspiration and collection of body tissue from within an enclosed body space

ABSTRACT

Device and method for rapid extraction of body tissue from an enclosed body cavity. Hollow entry cannula with optional core element provides entry into body tissue space such as bone marrow. Aspiration cannula is inserted through cannula into body tissue and is manipulated to advance directionally through body cavity. Optional stylet within aspiration cannula aids in advancing aspiration cannula through body tissue and is removed to facilitate extraction of body tissue through the aspiration cannula. Inlet openings near distal tip of aspiration cannula allow tissue aspiration, with negative pressure source at proximal end of aspiration cannula providing controlled negative pressure. Aspiration cannula may be withdrawn and its path adjusted for multiple entries through the same entry point, following different paths through tissue space for subsequent aspiration of more tissue.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.10/454,846 filed Jun. 04, 2003 which claims priority to U.S. ProvisionalApplication No. 60/384,998 filed Jun. 04, 2002, each of which isincorporated herein by reference in its entirety.

BACKGROUND

1. Field

Invention relates generally to the field of medicine and morespecifically to a device and method for rapid extraction of tissue froman enclosed body cavity.

2. Related Art

Bone Marrow is a rich source of pluripotent hematopoietic stem cellsfrom which red blood cells, white blood cells, and platelets are formed.Bone marrow also contains additional populations of cells which have thepotential to regenerate other tissues.

Since the early 1970's bone marrow and hematopoietic stem celltransplantation has been used to treat patients with a wide variety ofdisorders, including but not limited to cancer, genetic and autoimmunediseases. Currently over 400,000 transplants for a variety ofindications are performed worldwide each year.

In autologous transplants, the patient has their own bone marrowcollected prior to receiving high dose chemotherapy. Following highdose, myeloablative chemotherapy (which kills the majority of thepatients marrow stem cells) the stored autologous marrow (orhematopoietic stem cells purified or enriched from the marrow) isinfused, and serves to ‘rescue’ the patient's hematolymphoid system.

In allogeneic transplants bone marrow, or other sources of hematopoieticstem cells derived from a full or partially human leukocyte antigen(HLA) matched sibling, parent or unrelated donor is infused into therecipient patient and following engraftment, serves to reconstitute therecipients hematopoietic system with cells derived from the donor.

Following myeloablative or non-myeloablative conditioning of a patientwith chemotherapy and/or radiation therapy, the marrow is regeneratedthrough the administration and engraftment of hematopoietic stem cellscontained in the donor bone marrow.

In addition to hematopoietic stem cells and hematopoietic progenitors,bone marrow contains mesenchymal and other stem cell populations thoughtto have the ability to differentiate into muscle, myocardium,vasculature and neural tissues and possibly some organ tissues such asliver and pancreas. Recent research in preclinical animal studies (forexample Rafii S, et al., Contribution of marrow-derived progenitors tovascular and cardiac regeneration, Semin Cell Dev Biol 2002 February;13(1):61-7) and clinical trials (for example of recent clinical trialsand methods see Strauer B E, Wemet P. et al. Repair of infractedmyocardium by autologous intracoronary mononuclear bone marrow celltransplantation in humans. Circulation 2002 Oct. 8;106(15):1913-8, andthe article by Stamm C, ct al. Autologous bone-marrow stem-celltransplantation for myocardial regeneration. Lancet 2003 Jan. 4; 361(9351):45-6) suggest that bone marrow or some portion of the cellscontained within marrow can regenerate tissues other than thehematopoietic system. This includes the ability for cells containedwithin the marrow to regenerate or facilitate regeneration of myocardialtissue following a myocardial infarction, as evident by improved cardiacfunction and patient survival (Strauer BE, et al. Intracoronary, humanautologous stem cell transplantation for myocardial regenerationfollowing myocardial infarction, Dtsch Med Wochenschr 2001 Aug. 24;126(34-35):932-8).

Bone marrow derived stem cells also show evidence for their ability toregenerate damaged liver and hepatic cells (Lagasse E et al Purifiedhematopoietic stem cells can differentiate into hepatocytes in vivo,Nature Medicine 2000 November; 6(11):1229-34) and portions of thenervous system (Cuevas P et al. Peripheral nerve regeneration by bonemarrow stromal cells, Neurol Res 2002 October;24(7):634-8 Arthritis ResTher 2003;5(1):32A5) including spinal cord (Wu S et al Bone marrowstromal cells enhance differentiation of cocultured neurosphere cellsand promote regeneration of injured spinal cord. J Neurosci Res 2003 May1; 72(3):343-51.). Additional organ systems including kidney showbenefit from bone marrow derived cells (Poulsom R et al. Bone marrowstem cells contribute to healing of the kidney, J Am Soc Nephrol 2003June; 14 (Suppl 1):S48-54). Use of bone marrow and the stem cellscontained within bone marrow may be of increasing clinical utility inthe future treatment of patients.

Stem cells utilized in transplantation are primarily collected in one oftwo ways. First, by directly accessing the bone marrow (bone marrowharvest), in which marrow is removed from the patient, usually bymultiple aspirations of marrow from the posterior ileac crest, in a bonemarrow harvest procedure performed in the operating room. A secondcollection method is performed by removal of mononuclear cells from thedonor's peripheral blood (which contains a fraction of hematopoieticstem cells as well as other populations of cells including high numbersof T-cells. In this procedure peripheral blood stem cells are collectedby apheresis following donor treatment with either chemotherapy (usuallycyclophosphamide) or with the cytokine Granulocyte Colony StimulatingFactor (GCSF). Treatment with cyclophosphamide or GCSF functions tomobilize and increase the numbers of hematopoietic stern cellscirculating in the blood.

Traditional bone marrow harvest procedures have several shortcomings:

-   To perform a harvest of 500-1000 milliliters of marrow, multiple    separate entries into the marrow cavity are required to in order to    remove a sufficient amount of bone marrow. A bone marrow aspiration    needle (sharp metal trocar) is placed through the soft tissue,    through the outer cortex of the ileac crest and into the marrow    space. The aspiration needle enters less than 2 cm into the marrow    cavity. Negative pressure is applied through the hollow harvest    needle (usually by the operator pulling on an attached syringe into    which 5-10 ml of marrow is aspirated). The needle and syringe are    then removed and after removing the collected marrow, the aspiration    needle accesses a separate location on the ileac bone for another    aspiration. This is performed multiple times (on the order of    100-200 separate entries for an average patient) in order to remove    a sufficient volume of bone marrow required for transplantation.    Each puncture and entry into the marrow cavity accesses only a    limited area of the marrow space, and the majority of practitioners    only remove 5-10 milliliters of marrow with each marrow penetration.    Pulling more marrow from a single marrow entry site otherwise    results in a collected sample highly diluted by peripheral blood.-   General anesthesia—The bone marrow harvest procedure requires    general anesthesia. General anesthesia is required because the ileac    crest is penetrated 100-300 times with a sharp bone marrow trocar.    Local anesthesia is generally not possible given the large surface    area and number of bone punctures required.-   Recovery Time—The donor can take some time recovering from general    anesthesia, and frequently suffers from days of sore throat, a    result of the endotracheal intubation tube placed in the operating    room.-   Time consuming for patient—Pre-operative preparation, the harvest    procedure, recovery from anesthesia, and an overnight observation    stay in the hospital following the procedure is an imposition on the    donor.-   Time Consuming for the physician: In addition to general operating    room staff, the traditional bone marrow harvest procedure requires    two transplant physicians (each physician aspirating marrow from the    left or right side of the ileac crest) and. Who spend approximately    one hour each to perform the procedure.-   Pain—Many donors experience significant pain at the site of the    multiple aspirations (bone punctures) which persists for days to    weeks.-   Complications—Traditional bone marrow aspiration incurs a    significant degree of contamination with peripheral blood.    Peripheral blood contains high numbers of mature T-cells (unlike    pure bone marrow). T-cells contribute to the clinical phenomenon    termed Graft vs. Host Disease (GVHD), in both acute andchronic forms    following transplant in which donor T-cells present in the    transplant graft react against the recipient (host) tissues. GVHD    incurs a high degree of morbidity and mortality in allogeneic    transplants recipients.-   Expensive—Cost of the procedure $10-15K, which includes costs for    operating room time, anesthesia supplies and professional fees, and    post-operative care and recovery.

Peripheral Blood Stem Cell Collection also has several shortcomings:

-   Slow and time consuming—Requires the donor to first undergo 7-10 or    more days of daily subcutaneous injections with high doses of the    cytokine GCSF prior to the harvest. These daily injections can be    uncomfortable and painful. Peripheral blood stem cells can not be    obtained without this 7+ day lead time.-   Expense—Each day of apheresis costs approximately $3000 (including    but not limited to the cost of the apheresis machine, nursing,    disposable supplies and product processing) and the patient often    has to come back on multiple days in order to obtain an adequate    number of stem cells. Costs for the GCSF drug alone approximate    $6,000-10,000 depending upon the weight of the patient (usually    doses as 10 micrograms/kilogram/day).-   Complications—Given the multiple days required to collect adequate    numbers of hematopoietic stem cells, individual bags of peripheral    blood product must processed and frozen separately. These bags are    then thawed, and given back to the recipient patient at the time of    transplant. The volume, and chemicals contained in the product    freezing media can cause some mild side effects at the time of    infusion.

Accordingly, there is a need for a minimally invasive, less expensive,time-efficient bone marrow harvest procedure with minimal complicationswhich does not require general anesthesia, offers fast recovery time,and does not cause significant pain to the bone marrow donor.

SUMMARY

Device and method for rapid extraction of body tissue from an enclosedbody cavity. Device comprises a hollow introduction cannula containing atrocar. Entry cannula and core element penetrate body tissue such as themarrow space contained within the ileac or other bone. Aspirationcannula is inserted through entry cannula into body tissue and advancesthrough the body cavity. Within the aspiration cannula there may be astylet (aspiration stylet), which can aid in the advance of the cannulathrough cavity and can be removed to facilitate extraction of bodytissue through the aspiration cannula. Aspiration cannula has inletopenings near the distal tip through which tissue is aspirated. At theproximal end of aspiration cannula a negative pressure (suction) sourceprovides controlled negative pressure enabling tissue to be aspiratedthrough aspiration cannula into a collection reservoir. Aspirationcannula may be withdrawn and adjusted for multiple entries through thesame tissue entry point, following different paths through tissue spacefor subsequent aspiration of more tissue.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a diagram illustrating a device for rapid aspiration andcollection of body tissue from within an enclosed body space, accordingto one embodiment of the present invention.

FIG. 2 illustrates entry cannula 101 with core element 104, according toone embodiment of the present invention.

FIG. 3 illustrates aspiration cannula, according to an embodiment of thepresent invention.

FIG. 4 a shows aspiration cannula with one or more steering wires,according to an embodiment of the present invention.

FIG. 4 b shows perforated wall and cross-section of aspiration cannula,according to an embodiment of the present invention.

FIG. 4 c shows universal joint of aspiration cannula, according to anembodiment of the present invention.

FIG. 4 d shows squash plate of aspiration cannula, according to anembodiment of the present invention.

FIG. 4 e shows preset degree of curvature of aspiration cannula,according to an embodiment of the present invention.

FIG. 5 illustrates a groove cup, according to an embodiment of thepresent invention.

FIG. 6 a illustrates a distal tip, according to an embodiment of thepresent invention.

FIG. 6 b illustrates a sharp tip, a rotating drill tip and a sonicationdevice, according to an embodiment of the present invention.

FIG. 6 c illustrates a sonication device and an ultrasound transducer,according to an embodiment of the present invention.

FIG. 6 d illustrates an example of a distal tip modified to have arounded blunt tip, according to an embodiment of the present invention.

FIG. 7 illustrates inlet openings near the distal tip of aspirationcannula, according to an embodiment of the present invention.

FIG. 8 illustrates additional ports of aspiration cannula, according toan embodiment of the present invent ion.

FIG. 9 illustrates optional reservoir for materials or liquids foradministration, and optional electric motor, according to an embodimentof the present invention.

FIG. 10 a illustrates how the device for rapid aspiration and collectionof body tissue from within an enclosed body space enables a singleoperator to harvest marrow through one bone entry point, in accordancewith an embodiment of the present invention.

FIG. 10 b illustrates how a conventional bone marrow harvest procedureuses several bone punctures and separate small volume aspirations.

FIG. 11 illustrates a method for rapid aspiration and collection of bodytissue from within an enclosed body space, according to an embodiment ofthe present invention.

FIG. 12 shows entry site on one side of the body with multipleaspiration paths, according to an embodiment of the present invention.

DETAILED DESCRIPTION Overview

An apparatus is provided to aspirate bone marrow and/or tissue rapidlyand for large volumes of bone marrow from the ileac, femur, or othermarrow containing bone marrow cavities. The apparatus includes a lumenadapted to receive an elongated aspiration cannula. Following entrythrough the bone wall, the aspiration cannula may be controlled to movein a non-linear fashion within the marrow cavity so that it can access amajority of bone marrow space through a single point of entry. Suctionmay be applied to the aspiration cannula to harvest the bone marrow orother aspiratable substances. If it is determined that a thresholdamount of aspiratable substance has not been obtained, the aspirationcannula may be adjusted to enable further harvesting from the same bonewall entry or from an alternative bone wall entry.

Device and method for rapid, minimally invasive, aspiration andcollection of body tissue from within an enclosed body space, asdescribed herein, provide following advantages over the existing harvestsystems:

-   Efficacy—traditional extraction accesses only a small volume of    marrow with each needle insertion and negative pressure draws blood    from surrounding capillaries and dilutes the extract. Invention    described herein moves to directly contact more of the marrow space    and aspirates a more concentrated, less diluted extract. The    extracted bone marrow is more concentrated in stem cells because the    device penetrates the pelvic cavity more broadly and thus the    extracted material is less diluted with blood drawn into the void    created by the extraction. The decreased numbers of contaminating    T-cells will likely lead to less Graft vs. Host Disease (GVHD) in    allogeneic bone marrow recipients. Less total volume of bone marrow    will need to be removed (as it is more concentrated).-   Efficiency—the harvest performed with the invention described herein    proceeds faster than conventional trocar harvest because only one    access point into the marrow cavity is needed on each side of the    body and less total volume of material is extracted (as it is more    concentrated). One possible marrow access point is the easily    accessible anterior ileac crest access site, which is easier to find    and access on a broad array of patients (from thin to obese) and    utilizing this entry site will also reduce harvest time.-   Cost—the procedure described herein will be considerably less    expensive than the conventional procedure because described    invention requires no operating room time, reduced support    personnel, and no anesthesiologist. In terms of peripheral blood    hematopoietic stem cell aspiration via apheresis- the $6,000-$10,000    cost for GCSF cytokine treatments and several lengthy (4-20+ hours    each) apheresis procedures will be negated.-   Convenience: There is no significant lead or preparative time    required to perform a bone marrow harvest, as the procedure can be    performed without an operating room, or general anesthesia by a    single operator. Critically ill, or bone marrow donors who could not    readily tolerate traditional harvest methods would benefit. Marrow    and or stem cells derived from marrow could be obtained rapidly for    use in follow-on therapeutic interventions.    Qualities & Benefits:

This device and method could be applied to a range of soft tissueextractions. Specific uses include, but are not limited to, theaspiration of bone marrow, removal of fat, aspiration of blood andmuscle. We consider the bone marrow harvest application further for thesake of illustration.

-   To provide a bone marrow aspiration device for the rapid extraction    of small or large volumes of bone marrow from the ileac, femur or    other marrow containing bone marrow cavities or spaces.-   To aspirate tissue such as marrow through a single skin and bone    puncture site into the marrow cavity.-   The ability to control directionality of described invention within    the marrow cavity such that it can access majority of bone marrow    space through a single point of entry.-   To provide controlled aspiration suction through described invention    of bone marrow or other aspiratable substance such as fat.-   Described invention will significantly shorten bone marrow harvest    time, not require general anesthesia, and result in cost reductions    compared to traditional bone marrow harvest of peripheral blood stem    cell collection.-   To enable access to multiple diagnostic samples of bone marrow from    disparate sites within the marrow cavity

FIG. 1 is a diagram illustrating a device 100 for rapid aspiration andcollection of body tissue from within an enclosed body space(hereinafter referred to as “aspiration device”), according to oneembodiment of the present invention. Aspiration cannula 105 couples tooptional handle 102 for ease of holding and operation.

FIG. 2 illustrates entry cannula 101 with core element 104, according toone embodiment of the present invention. Entry cannula 101 comprises aneedle with hollow central lumen accommodating a core element 104 forinitial insertion into a bone marrow cavity or body tissue, for examplethrough the anterior ileac crest, posterior ileac crest, lateraltrocanter of the femur, or other location for aspiration bone marrow orother body tissue. Aspiration cannula 105 enters the body tissue throughthe entry provided by entry cannula 101.

Core element 104 comprises a trocar or other element for breaking orpiercing through the bone wall (or other tissue boundary) and creatingan entry for subsequent aspiration. Optionally, entry cannula 101 isstrong enough to break or pierce through the bone wall without the helpof core element 104.

In an alternative embodiment, an entry in the bone wall is created usinga tool other than entry cannula 101 and/or core element 104, such as aseparate trocar or other sharp tool for breaking or piercing the bonewall, preparing the bone (or other tissue area) for the entry ofaspiration cannula 105.

Once an entry is created into the bone marrow and entry cannula 101enters the bone marrow (or other body tissue intended for aspiration),core element 104 is removed, leaving a hollow entry lumen with access tothe medullary cavity.

FIG. 3 illustrates aspiration cannula 105, according to an embodiment ofthe present invention. Aspiration device 100 comprises aspirationcannula 105, for entering through the hollow entry cannula 101 andthrough the bone wall (or other tissue area) entry into the marrowspace. Aspiration cannula 105 comprises flexible material allowing forcurvature for following bone marrow cavity (or other tissue area). Inone embodiment, aspiration cannula 105 has a length of 6-16 inches. Thesize of the aspiration cannula 105 may vary based on the size andanatomy of the patient and/or the bone marrow cavity (or other bodytissue area) intended for harvest.

Aspiration cannula 105 optionally comprises a stylet 106 (“aspirationstylet”). When inserted into aspiration cannula 105, optional aspirationstylet 106 provides structural strength and aids in (for example theintramedullary bone marrow space of the ileac or femur bone) advance ofaspiration cannula 105 through the marrow space (or other tissue area).Optionally, aspiration stylet 106 comprises a preset degree of curvatureprior to and following entry into body cavity through entry cannula 101.Aspiration stylet 106 can be removed from aspiration cannula 105 toallow aspiration of marrow (or other body tissue) through aspirationcannula 105. Optionally, aspiration stylet 106 is used to remove and/ordisrupt blockages within aspiration cannula 105, such as bone fragments,fat, coagulation, blood clots or other substance which may be blockingaspiration.

Optionally, aspiration cannula 105 is steerable and directable. FIG. 4 ashows aspiration cannula 105 equipped with one or more steering wires107, according to an embodiment of the present invention. Contraction orpulling of a steering wire 107 by operator results in curvature ofaspiration cannula 105 according to the direction and/or location ofcontracted or pulled steering wire 107. Optionally, and as shown in FIG.4 b aspiration cannula 105 comprises flexible material and/orperforations 108 on the wall of aspiration cannula 105 allowing forcurvature and increased lateral flexibility, and/or oval cross-sectionfor limiting axes of curvature. Optionally, aspiration cannula 105comprises material with shape-memory, for example a shape memory alloy(such as Nitinol), a shape memory plastic, or other metallic ornon-metallic material with shape-memory, for example resulting in acurved profile of aspiration cannula 105, for providing directionalityto aspiration cannula 105 upon aspiration cannula's 105 entry into thebody tissue or body cavity.

Optionally, as shown in FIG. 4 c, aspiration cannula 105 comprises auniversal joint 109 for providing a pivot point, allowing thecontraction or pulling of steering wires 107 to result in steeringand/or change of direction of aspiration cannula 105.

Optionally, as shown in FIG. 4 d, aspiration cannula 105 comprises asquash plate 110, allowing the contraction or pulling of steering wires107 to result in steering and/or change of direction of aspirationcannula 105.

Optionally, as shown in FIG. 4 e, aspiration cannula 105 a preset degreeof curvature such that after passing through entry cannula 101 and intothe bone cavity, aspiration cannula 105 assumes a curvature according tothe preset curvature, thereby assisting its direction when advancingwithin the cavity.

Optionally and as illustrated in FIG. 5, a groove cup 120 is used forguiding aspiration cannula 105 into bone marrow (or other body tissue).Groove cup 120 comprises one or more grooves 121, a groove 121 providingdirectional entry of aspiration cannula 105 into bone marrow. Placementof aspiration cannula 105 into an appropriate groove 121 allows entry ofaspiration cannula 105 into bone marrow with directionality according toselected groove 121. Optionally, groove cup 120 has groove dial 122 forconvenient selection of groove 121 and guiding of aspiration cannula 105through selected groove 121 and into the bone marrow space.

According to one embodiment of the present invention and as shown inFIG. 6 a, aspiration device 100 comprises a distal tip 130 at the distalend of aspiration cannula 105 or at the distal end of optionalaspiration stylet 106, for advancing through the bone marrow cavity (orother body tissue).

As shown in FIG. 6 b, Distal tip 130 comprises a sharp tip 131, arotating drill tip 132 (manual or powered, for example powered by anelectric motor 162 as shown in FIG. 9, with motor 106 using power frombatteries 163 or from an outside electrical source), optionallycomprising a variable speed controllable and/or reversible drill tip), asonication device 133 (for tissue disruption) or other tissue disrupterfor penetrating and/or advancing through the bone marrow (or other bodytissue).

Optionally and as shown in FIG. 6 c, distal tip 130 comprises anultrasound transducer or other navigation element 134 for providingnavigation and/or visual guidance within bone marrow space (or otherbody tissue) to assist steering of aspiration cannula 105, such asproviding feedback indicating proximity of distal tip 130 or aspirationcannula 105 to bone wall (or to other tissue boundary).

Optionally, distal tip 130 is modified such that it cannot puncture outof the body space or cavity (such as bone marrow space or other bodytissue area) but instead moves sideways along a wall or boundary uponencountering such wall or boundary. FIG. 6 d shows an example of adistal tip 130 modified to have a rounded blunt tip 135 to behave inthis way.

Optionally, aspiration device 100 comprises a combination ofradio-opaque and/or radio-transparent material for use in conjunctionwith an imaging device, such as an X-ray or ultrasound device, forvisual location of the aspiration cannula 105. For example, aspirationcannula 105 and/or other parts may be radio-transparent, with aspirationcannula 105 comprising a radio-opaque visual guide (for example usingX-Rays or other radiographic methods) along the length of aspirationcannula 105 (such as a strip with visual distance markings showing howfar aspiration cannula 105 has advanced into bone marrow space or otherbody tissue area).

As shown in FIG. 7 according to one embodiment of the present invention,aspiration cannula 105 comprises one or more inlet openings 150 near thedistal tip 130 through which marrow or other tissues can be aspirated bythe application of negative pressure. A negative pressure elementcouples to the proximal end of aspiration cannula 105 for application ofnegative pressure resulting in aspiration (suction) of bone marrow (orother body tissue) into a reservoir for bone marrow (or for other bodytissue). In one embodiment, the negative pressure element comprises asyringe. In another embodiment, the negative pressure element comprisesa powered device (such as a wall mounted continuous negative pressuredevice or other powered device for providing controlled negativepressure). Handle 102 has optional trigger element 103 (as shown in FIG.9) for controlling aspiration negative pressure or degree of suction,for example by controlling a pressure gate for allowing proper degree ofnegative pressure.

Optionally, aspiration device 100 comprises a pain attenuating devicefor dampening pain and/or sensation during the aspiration procedure. Forexample, aspiration cannula 105 may comprise one or more sites forproviding electrical nerve stimulation to the harvest area resulting inpain attenuation (see U.S. Pat. No.6,159,163, Strauss et al., May 1998).

Optionally, a lining of anticoagulant material (such as heparin) on theinside wall of entry cannula 101 and/or aspiration cannula 105 preventsblood and/or marrow from coagulating and hindering aspiration of marrowor body tissue. Optionally, entry cannula 101 and/or aspiration cannula105 are flushed with anticoagulant solution to prevent and/or dissolveclots.

Optionally and as shown in FIG. 8, aspiration cannula 105 has one ormore additional ports 160 through which material or liquid (such asanticoagulant described above) can be administered. An optional port inthe aspiration cannula 105 allows administration of a stylet into theaspiration cannula for unblocking or removing any blood or tissue clotswhich may occur. Aspiration device 100 comprises optional reservoir 161for materials or liquids (such as anticoagulant described above) foradministration, as shown in FIG. 9.

FIG. 9 also shows an example of a steering control 140 for steering,guiding, advancing, and/or retracting aspiration cannula 105 whileaspiration cannula 105 in outside and/or inside bone marrow space (orother body tissue area). In the embodiment described above, whereinaspiration cannula 105 comprises one or more steering wires 107,activation of steering control 140 causes contraction or pulling of oneor more steering wires 107 resulting in curvature and/or change ofdirection of aspiration cannula 105. In one embodiment, steering control140 comprises a manual control, such as a handle, which can be moved tosteer or manipulate aspiration cannula 104. For example, forwardmovement of apparatus 100 causes advancement of aspiration cannula 105and backward movement of apparatus 100 results in withdrawal ofaspiration cannula 105, whereas movement of steering control 140 handleto different -sides (for example to the left, right, up or down) causesaspiration cannula 105 to curve to the corresponding side (for exampleto the left, right, up or down). In another embodiment, steering control140 comprises a powered control, such as a multi-way thumb-stick or oneor more buttons for steering and/or advancing and retracting aspirationcannula 105 (shown in FIG. 9).

The length and/or diameter and/or flexibility and/or curvature of entrycannula 101 and/or aspiration cannula 105 can be chosen to accommodatedifferent anatomies (such as corresponding to different ages, bonesizes, amount of body fat, and other factors distinguishing patients)and for the harvest of a range of body tissues, such as bone marrow, fat(liposuction), fluid in the abdomen of a patient (with liver disease forexample), or possibly for minimally invasive removal of a soft tissuemass such as a tumor. For example, a child may require a shorter, moreflexible aspiration cannula 105. As another example, aspiration of bonethrough the lateral trocanter of the femur, or via the anterior ileaccrest may require a shorter entry cannula 101 and/or aspiration cannula105 than aspiration of bone marrow through the posterior ileac crestwhich may have more soft tissue above the bone.

There is growing body of scientific evidence that bone marrow derivedstem cells can be utilized to regenerate or improve function of damagedmyocardium following a myocardial infarction (MI), and may be useful intreating and preventing congestive heart failure. The ability to rapidlyand easily obtain bone marrow derived stem cells for use in cardiacregeneration and other regenerative stem cell based therapies may becrucial. For example; a patient who has recently been diagnosed with asignificant myocardial infarction is brought to the catheterizationsuite, where interventional cardiologists perform angioplasty to open upa blocked coronary artery. Before, during or after the angioplastyprocedure, a significant volume of bone marrow would be harvested usingaspiration device 100. The bone marrow could be rapidly processed toenrich for hematopoietic stem cells or other populations or fraction ofcells contained within bone marrow. These cells would then be deliveredvia catheter of other delivery device to the region of the heart whichhas undergone infarction and injury or death secondary to acute cardiacischemia or other acute or chronic insults to the myocardial tissue. Thedelivered bone marrow or stem cell component contributes to regenerationof the myocardium or otherwise acts to improve cardiac function in thearea of the infarct and leads to improved cardiac function and patientfunctional status and mortality. Optionally, marrow could be harvestedseparately from the initial cardiac catheterization procedure (forexample 7 days after the MI, and in a separate procedure, stem cells ormarrow enriched for stem cells could he delivered by any number ofdelivery mechanisms, for example by intracoronary or intramuscularinjection. Use of a minimally invasive harvest device 100 wouldfacilitate ease of harvest in patients who may be critically ill and notable to easily tolerate traditional marrow harvest procedures.

Advantageously, aspiration device 100 considerably improves on existingbone marrow harvest procedures by enabling a single operator to harvestmarrow through one bone entry point, as illustrated in FIG. 10 a,instead of several dozen to hundreds of bone punctures and separatesmall volume aspirations, as shown in FIG. 10 b.

FIG. 11 illustrates a method for rapid aspiration and collection of bodytissue from within an enclosed body space, according to an embodiment ofthe present invention. After providing 200 an entry into the marrowusing entry cannula 101 (and/or using core element 104, in which casethe core element 104 of the entry cannula 101 is removed after providingthe entry), a hollow entry lumen is left with access to the medullarycavity. Next, aspiration cannula 105 is placed 201 through the hollowentry cannula 101 and introduced into the marrow space. The aspirationcannula 105 is then manipulated 202 (using steering control 140) to moveand follow the bone marrow cavity, assisted by the distal tip 130 theaspiration cannula.

As described above, aspiration cannula 105 will have a degree offlexibility and/or curvature allowing it to follow the cavity (forexample the intramedullary bone marrow space of the ileac or femurbone), and an optional ultrasound transducer device at the distal tip130 of the aspiration cannula 105 can aid movement and define width ofthe cavity.

Once the aspiration catheter is fully introduced into the body cavity,negative pressure is initiated 203, using for example a syringe or apowered negative pressure device as described above. As bone marrow isaspirated the aspiration cannula 105 is slowly withdrawn 204, withaspiration continuing as the aspiration cannula 105 is withdrawn. If 205sufficient amount of bone marrow is aspirated 205, the aspirationprocess is complete 206. Otherwise 207, after withdrawal of aspirationcannula 105, the curvature and/or directionality of the aspirationcannula 105 is adjusted 208, and aspiration cannula 105 is redirectedthrough the entry into the bone marrow space and manipulated to follow adifferent path through the space and aspirating more bone marrow. Thisprocess can be repeated for example 3-4 times, resulting in itsaspiration of bone marrow from the majority of the bore marrow space(for example the ileac crest). This process can be repeated 011 bothsides of the body as needed (FIG. 12 shows an entry site on one side ofthe body with multiple aspiration paths).

As described above, there is the option of utilizing one or moreaspiration cannula 105 with preset or modifiable degrees of curvatureand/or length and/or diameter and/or flexibility to adapt to differentindividual patients' anatomy and degree of ileac or other bone anatomy.As described above, aspirated bone marrow will go directly into bonemarrow reservoir or container through a closed system for initialstorage and/or follow-on manipulation (such as filtering, stem cellenrichment, or other follow-on manipulation or treatment of bonemarrow).

The apparatus and method shown herein provide many advantages for rapidaspiration and collection of body tissue from within an enclosed space.The directional control of the aspiration cannula by the operatorenables the cannula to directly contact more of the marrow space andthereby aspirate a bone marrow that is more concentrated with stem cellsthan that available in the prior art. In addition, the harvest performedwith the apparatus shown herein proceeds faster than prior artharvesting with a trocar since only one access point is required on eachside of the body and less total volume of material is extracted.Finally, the procedure outlined above requires less time and reducedsupport personnel, thereby reducing costs for a procedure for harvestingbone marrow and/or tissue.

Foregoing described embodiments of the invention are provided asillustrations and descriptions. They are not intended to limit theinvention to precise form described. Other variations and embodimentsare possible in light of above teachings, and it is thus intended thatthe scope of invention not be limited by this Detailed Description, butrather by Claims following.

1. A method for aspirating body tissue, comprising: introducing anaspiration cannula having a flexible length into the body tissue throughan entry port defined along a body cavity containing the body tissue;advancing the aspiration cannula along a first path within the bodytissue; withdrawing the aspiration cannula proximally along the firstpath; while withdrawing, aspirating a first portion of the body tissueinto the aspiration cannula via one or more openings in a distal tip orproximal thereto; and advancing the aspiration catheter along a secondpath within the body tissue, wherein the second path is different fromthe first path.
 2. The method of claim 1 wherein introducing comprisespiercing through a cortical layer of bone wall of the body cavity. 3.The method of claim 2 wherein piercing through a bone wall comprisespiercing via an entry cannula through which the aspiration cannula isintroduced.
 4. The method of claim 1 wherein advancing the aspirationcannula along a first path comprises directing the distal tip to followthe first path.
 5. The method of claim 1 wherein advancing theaspiration cannula along a first path comprises inhibiting the distaltip from puncturing through a wall of the body cavity such that theaspiration cannula is retained within the body cavity.
 6. The method ofclaim 1 wherein advancing the aspiration cannula along a first pathcomprises inhibiting the distal tip from puncturing through a corticallayer of bone such that the aspiration cannula is retained within amedullary cavity.
 7. The method of claim 1 wherein aspirating a firstportion comprises aspirating bone marrow into the aspiration cannula,the bone marrow being contained within a bone of a patient body.
 8. Themethod of claim 1 wherein advancing the aspiration catheter along asecond path comprises directing the distal tip to follow the secondpath.
 9. The method of claim 8 further comprising withdrawing theaspiration cannula proximally along the second path.
 10. The method ofclaim 9 further comprising while withdrawing, aspirating a secondportion of the body tissue into the aspiration cannula via one or moreopenings in a distal tip or proximal thereto.
 11. A method foraspirating bone marrow, comprising: introducing an aspiration cannulahaving a flexible length into the bone marrow through an entry portdefined along a bone cavity containing the bone marrow; advancing theaspiration cannula along a first path within the bone marrow;withdrawing the aspiration cannula proximally along the first path;while withdrawing, aspirating a first portion of the bone marrow intothe aspiration cannula via one or more openings in a distal tip orproximal thereto; and advancing the aspiration catheter along a secondpath within the bone marrow, wherein the second path is different fromthe first path.
 12. The method of claim 10 wherein advancing theaspiration cannula along a first path comprises directing the distal tipto follow the first path.
 13. The method of claim 11 wherein advancingthe aspiration cannula along a first path comprises inhibiting thedistal tip from puncturing through a wall of cortical bone such that theaspiration cannula is retained within a medullary cavity.
 14. The methodof claim 11 wherein advancing the aspiration catheter along a secondpath comprises directing the distal tip to follow the second path. 15.The method of claim 14 further comprising withdrawing the aspirationcannula proximally along the second path.
 16. The method of claim 15further comprising while withdrawing, aspirating a second portion of thebone marrow into the aspiration cannula via one or more openings in adistal tip or proximal thereto.